Challenges remain to ensure the efficient and targeted delivery of agents across the blood brain barrier by invasive and non-invasive delivery methods to a provide flexible, reproducible and cost-effective method of managing CNS disorders

Many new classes of drugs will reach the market over the next 6 years, driving future market growth including small molecules, peptides and regenerative therapies (stem cells and gene therapies). Their success is analyzed in detail and case studies provided to highlight the progress of each technology.

The application of nanotechnologies including micellar nanoparticles, nanoparticles, nanocells and lipobridge systems offers significant opportunities for selective and targeted delivery of CNS products. A number of nano-enabled delivery systems are evaluated in this report.

As the CNS market evolves new approaches to treatment of CNS are emerging utilizing stem cells and gene-based therapies. Several companies are working towards this goal including: Copernicus Therapeutics, Genzyme, Oxford Biomedica, NeuroGeneration and Pharmidex. A number of delivery options are currently being evaluated to optimize the clinical utility of these regenerative therapies and are analyzed in detail in the report.

Introduction

“The World Health Organization has indicated that CNS disorders are the major medical challenge of the 21st Century, yet treatments for most CNS disorders are either inadequate or absent. The CNS is the most challenging frontier for drug discovery largely because of the complexity of the brain and the existence of the BBB”

Alan Palmer, Chief Executive of Pharmidex, UK

The revenue derived from Central Nervous System (CNS) drugs is vast, in that such a large number of diseases and disease processes are grouped under the CNS “umbrella”. These include acute organic conditions, such as infection, pain (both acute and chronic); chronic organic conditions such as neoplasms, seizure disorders; chronic degenerative disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and other dementias, as well as the range of functional disorders classified as mental illnesses: schizophrenia, affective and anxiety spectrum disorders, attention deficit hyperactivity disorder (ADHD), sleep disorders and addictions.

The CNS has always posed problems in terms of drug delivery, drug efficacy and safety/ tolerability because of the presence of the blood brain barrier (BBB). The BBB is composed of a layer of extremely tightly packed epithelial cells, saturated with enzymes designed to protect the brain by disallowing the entry of noxious substances via the bloodstream. The unfortunate by-product of this has been the problem of delivering beneficial drugs to the CNS in sufficient quantities to effectively treat the targeted condition without causing unacceptable systemic adverse reactions.

Administering drugs directly into the CNS e.g. intrathecally or intracerebrally, is an effective method of delivery but carries significant risks in terms of infection as well as being invasive and unpleasant for the patient. In recent years, methods of by-passing the BBB have been proposed, trialed and are now available, such as osmotic permeability, the use of nanoparticles small enough to penetrate the BBB, ultrasonic adjunctive drug treatment, and stem-cell and gene therapy, which effectively provide a “self-cure” by promoting neuroplasticity and cell regeneration within the central nervous system itself.

Newer delivery methods such as transdermal drug delivery which can employ nanotechnology to increase absorption and bioavailability, as well as being non-invasive and simple to use are on the rise, and seem set to be used for a wide range of CNS disorders, including psychoses, pain and neurodegenerative disorders.

SEVEN QUESTIONS THIS NOTE ANSWERS:

1. How will the drug delivery technology drivers change in the CNS arena during the next decade and beyond?
2. What are the key delivery technologies and devices in the CNS field?
3. When are products and medical devices which utilize these key delivery echnologies likely to reach the market?
4. Which drug delivery technologies are likely to win in the near-term and the ong-term, and why?
5. Which companies are the winners in each technology category?
6. How are drug delivery technologies evolving to meet the demands of the CNS market?
7. Where are the market opportunities now and in the future?